Effects of KRAS (G13C) expression on transcriptome profiles assessed in HPCs differentiated from patient-derived iPS cells

How a single oncogenic RAS impacts non-transformed hematopoietic progenitor cells (HPCs) remains largely unknown. We therefore investigated how a monoallelic KRAS mutation (G13C) affected HPCs utilizing induced pluripotent stem cells (iPSCs) derived from two unrelated patients with RAS-associated autoimmune lymphoproliferative syndrome-like disease (RALD). We performed gene expression profiling analysis of 12 HPC samples in total, with 6 samples being from each patient. The two clones from each patient constituted an isogenic pair of different genotypes (WT/WT and WT/G13C). Three samples obtained from each clone were subjected to the analysis, one with no stimulation, and the other two each stimulated with different cytokine combinations.